Friday, April 28, 2017

Chronic calcium blocker use and reduced mortality in sepsis

From a recent paper:


Objectives: Experimental studies suggest that calcium channel blockers can improve sepsis outcome. The aim of this study was to determine the association between prior use of calcium channel blockers and the outcome of patients admitted to the ICU with sepsis.

Design: A prospective observational study.

Setting: The ICUs of two tertiary care hospitals in the Netherlands.

Patients: In total, 1,060 consecutive patients admitted with sepsis were analyzed, 18.6% of whom used calcium channel blockers.

Interventions: None.

Measurements and Main Results: Considering large baseline differences between calcium channel blocker users and nonusers, a propensity score matched cohort was constructed to account for differential likelihoods of receiving calcium channel blockers. Fifteen plasma biomarkers providing insight in key host responses implicated in sepsis pathogenesis were measured during the first 4 days after admission. Severity of illness over the first 24 hours, sites of infection and causative pathogens were similar in both groups. Prior use of calcium channel blockers was associated with improved 30-day survival in the propensity-matched cohort (20.2% vs 32.9% in non-calcium channel blockers users; p = 0.009) and in multivariate analysis (odds ratio, 0.48; 95% CI, 0.31–0.74; p = 0.0007). Prior calcium channel blocker use was not associated with changes in the plasma levels of host biomarkers indicative of activation of the cytokine network, the vascular endothelium and the coagulation system, with the exception of antithrombin levels, which were less decreased in calcium channel blocker users.

In the discussion section the authors mention a possible mechanism:

Here, we show a significantly reduced mortality in ICU patients who were on chronic CCB treatment before development of sepsis. The association between prior CCB use and reduced sepsis mortality was consistent in sensitivity and subgroup analyses. The mechanism by which chronic CCB use may influence sepsis outcome was not revealed by sequential measurements of host response biomarkers reflecting activation of the cytokine network, the vascular endothelium or the coagulation system, and rather may involve partial prevention of cellular toxicity related to sustained elevations in intracellular Ca2+ levels.

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